Natl Conf Hum Retroviruses Relat Infect (1st). 1993 Dec 12-16;:133.

OM-10.1 cells were derived by Butera and coworkers from the human promyelocyte cell line HL-60 following coculture with HIV-1 infected gamma-irradiated T-lymphocytes. Although they constitutively express HIV-1 at very low levels, treatment of the cells with TNFalpha rapidly induces HIV expression to a high level. Similar to Schinazi and coworkers, we have been using OM-10.1 cells to evaluate the antiviral activity of compounds against the late events of HIV-1 replication. Since these cells are CD4+ and readily susceptible to superinfection, the conditions used for cell passage become very important. Using p24 antigen as a marker of virus expression, we have determined the baseline of expression to be less than 1 ng/ml. Within 24 hours after TNFalpha induction the p24 level increased to about 100 ng/ml, and it was near 1000 ng/ml by 72 hours. A corresponding increase in the presence of infectious virus was also identified. However, if cells were not continuously grown in the presence of an antiviral agent (such as AZT or ddI) the baseline p24 level increased. Two important assay parameters are the length of treatment of the cells with test drugs prior to TNFalpha induction, and the concentration of TNFalpha used. An inhibitor of the HIV-1 protease was found to efficiently reduce p24 expression after a 6 hour pretreatment and induction with low as well as high doses of TNFalpha. Pretreatment for 24 hours did not further enhance the antiviral effect. An inhibitor of the HIV-1 Tat function, however, required the longer pretreatment time, as well as the lower dose of TNFalpha, in order to achieve its best antiviral activity.

Antiviral Agents/PHARMACOLOGY Cells, Cultured Drug Synergism Human HIV-1/*DRUG EFFECTS/ENZYMOLOGY/PHYSIOLOGY Macrophages/*VIROLOGY Monocytes/*VIROLOGY RNA-Directed DNA Polymerase/ANTAGONISTS & INHIB Virus Replication/DRUG EFFECTS ABSTRACT